Biopolymer arrays such as polynucleotide arrays (for example, DNA or RNA arrays), are known and are used, for example, as diagnostic or screening tools. Such arrays include regions of usually different sequence polynucleotides arranged in a predetermined configuration on a substrate. These regions (sometimes referenced as “features”) are positioned at respective locations (“addresses”) on the substrate. The arrays, when exposed to a sample, will exhibit an observed binding pattern. This binding pattern can be detected upon interrogating the array. For example all polynucleotide targets (for example, DNA) in the sample can be labeled with a suitable label (such as a fluorescent compound), and the fluorescence pattern on the array accurately observed following exposure to the sample. Assuming that the different sequence polynucleotides were correctly deposited in accordance with the predetermined configuration, then the observed binding pattern will be indicative of the presence and/or concentration of one or more polynucleotide components of the sample.
Biopolymer arrays can be fabricated by depositing previously obtained biopolymers onto a substrate, or by in situ synthesis methods. The in situ fabrication methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, and in U.S. Pat. No. 6,180,351 and WO 98/41531 and the references cited therein for synthesizing polynucleotide arrays. Further details of fabricating biopolymer arrays are described in U.S. Pat. No. 6,242,266, U.S. Pat. No. 6,232,072, U.S. Pat. No. 6,180,351, and U.S. Pat. No. 6,171,797. Other techniques for fabricating biopolymer arrays include known light directed synthesis techniques.
In array fabrication, the probes formed at each feature is usually are expensive. Additionally, sample quantities available for testing are usually also very small and it is therefore desirable to simultaneously test the same sample against a large number of different probes on an array. These conditions make it desirable to produce arrays with large numbers of very small (for example, in the range of tens or one or two hundred microns), closely spaced features (for example many thousands of features). After an array has been exposed to a sample, the array is read with a reading apparatus (such as an array “scanner”) which detects the signals (such as a fluorescence pattern) from the array features. Such a reader should typically have a very fine resolution (for example, in the range of five to twenty microns).
The array image resulting from reading the array can then be digitally processed to evaluate which regions (pixels) of read data belong to a given feature as well as the total signal strength from each of the features. The foregoing steps, separately or collectively, are referred to as “feature extraction”. However, the signal from many pixels may be so low that it is difficult to decide whether a given pixel belongs to a given feature without having knowledge of the location of that feature in the image. This can be a difficult task since in any batch of even the same arrays, features may be displaced to some small degree relative to each other, the exact array positioning on a substrate may vary slightly, or the positioning of the substrate in a reader may vary slightly. Any of these conditions can cause features to be displaced in the array image from an expected location. Thus, in some procedures for accurately determining feature locations in the image, user input is required to accurately pinpoint on a display of the image at least some features from which the locations of other features can be deduced. For example, the user may be asked to select a center point of corner features in the array image. However, since an array can easily contain ten thousand or more features, the features on a complete image of the array on a typical display will appear as points at best, or worse will not even be visible. This makes user pinpointing of a location of some features in the displayed image, such as by selecting the center of corner features, difficult and prone to error. Of course, a user can zoom in on a portion of the array image, pinpoint a feature location (such as a feature center), zoom out, zoom in on another portion of the image, pinpoint another feature location, then repeat this tedious procedure as often as needed.
It would be desirable then, in determining feature locations in an array image where user input is required to accurately pinpoint locations of some features, to provide a means which does not require a large number of tedious steps from the user.